A hallmark of several cancer types, including melanoma, is increased
telomerase activation. Telomerase is an enzyme responsible for
elongating telomeres which protect the integrity of chromosome ends
during cell replication. While absent in most normal cells, telomerase
is highly active in cancer cells, driving continuous cell divisions.

“Telomerase is an almost universal oncology target. In the present
study, we provide a scientific rationale for the development of new
clinical cancer treatments based on targeting telomeres in cancer
cells,” said Jerry W. Shay, co-author of the study, and professor of
Cell Biology at UT Southwestern Medical Center.

Meenhard Herlyn, D.V.M., D.Sc., Caspar Wistar Professor in Melanoma
Research and director of The Wistar Institute Melanoma Research Center,
and his collaborators used a modified telomerase substrate they had
previously described, 6-thio-2’-deoxyguanosine or 6-thio-dG (THIO), to
utilize telomerase to induce telomere dysfunction. They demonstrated
that THIO induced cell death in melanoma cells harboring BRAF gene
mutations and impaired tumor growth in several BRAF-mutant mouse
melanoma models without affecting the viability of normal skin cells.

The team also studied the ability of THIO treatment to stop
proliferation and tumor growth of therapy-resistant melanoma cells. They
created a large panel of human melanoma cell lines with acquired
resistance to targeted therapy and immunotherapy and showed a general
sensitivity of these cells to THIO both in vitro and in vivo.

“These exciting results add to a substantial amount of scientific data
on THIO supporting our development program,” said Frank Perabo, CEO of
Barricade Therapeutics. “The data suggest that THIO could be studied in
future clinical trials in a first- and second-line therapy setting, or
in combination with other agents to overcome intrinsic resistance.”

This work was supported by grants from NIH, DoD, Dr. Miriam and Sheldon
G. Adelson Medical Research Foundation and the Melanoma Research
Foundation.

About THIO:

THIO (6-thio-2′-deoxyguanosine or 6-thio-dG) specifically targets and
induces damage to telomeric DNA, resulting in the selective death of
tumor cells. Telomerase is an almost universal driver of tumor growth.
THIO utilizes a novel mechanism of action, and in contrast to other
telomerase inhibitor–based approaches, THIO is not a direct telomerase
inhibitor. THIO causes telomere uncapping, leading to cancer cell death.
Barricade Therapeutics is developing THIO for multiple oncology
indications and has licensed the global exclusive rights from UT
Southwestern, Dallas, TX.

About Barricade Therapeutics:

Barricade Therapeutics, Corp. (www.barricadetherapeutics.com)
is a privately-held Biotech company based in Houston, TX. Barricade was
founded based on discovery and advancement of novel first-in-class
anti-cancer small molecules. The current status of the development
programs is preclinical.